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Erschienen in: Journal of Assisted Reproduction and Genetics 2/2018

30.10.2017 | Genetics

Chromosomal abnormalities in products of conception of first-trimester miscarriages detected by conventional cytogenetic analysis: a review of 1000 cases

verfasst von: Larysa Y. Pylyp, Lyudmyla O. Spynenko, Nataliya V. Verhoglyad, Anna O. Mishenko, Dmytro O. Mykytenko, Valery D. Zukin

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 2/2018

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Abstract

Purpose

The purpose of this study is to perform a retrospective analysis of types and frequencies of chromosomal abnormalities detected by conventional cytogenetic studies in first-trimester miscarriages after spontaneous conception and IVF.

Methods

Standard cytogenetic analysis of GTG-banded chromosomes obtained from products of conception (POCs): semi-direct and short-term cultured chorionic villi or long-term cultured fetal mesodermal cells.

Results

50.1% of first-trimester miscarriages in the studied group had chromosomal abnormalities: 59.7% of trisomies, 22% of poliploidies, 7.5% of monosomies, 7% of unbalanced structural abnormalities, and 3.8% of multiple aneuploidies. An increase in the frequency of chromosomally abnormal miscarriages was observed in the group of women above 40 when compared to groups of women under 35 (P < 0.05). No difference in frequencies and types of chromosomal abnormalities in POCs of miscarriages after ICSI and spontaneous conception was observed.

Conclusions

Approximately, 50% of first-trimester miscarriages have chromosomal abnormalities which can be detected by conventional cytogenetic analysis. The presence of chromosomal abnormality may explain the cause of miscarriage, improving the reproductive counseling and planning.
Literatur
1.
Zurück zum Zitat van den Berg MM, van Maarle MC, van Wely M, Goddijn M. Genetics of early miscarriage. Biochim Biophys Acta. 2012;12:1951–9.CrossRef van den Berg MM, van Maarle MC, van Wely M, Goddijn M. Genetics of early miscarriage. Biochim Biophys Acta. 2012;12:1951–9.CrossRef
2.
Zurück zum Zitat Jenderny J. Chromosome aberrations in a large series of spontaneous miscarriages in the German population and review of the literature. Mol Cytogenet. 2014;7:38.CrossRefPubMedPubMedCentral Jenderny J. Chromosome aberrations in a large series of spontaneous miscarriages in the German population and review of the literature. Mol Cytogenet. 2014;7:38.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Wu T, Yin B, Zhu Y, Li G, Ye L, et al. Molecular cytogenetic analysis of early spontaneous abortions conceived from varying assisted reproductive technology procedures. Mol Cytogenet. 2016;9:79.CrossRefPubMedPubMedCentral Wu T, Yin B, Zhu Y, Li G, Ye L, et al. Molecular cytogenetic analysis of early spontaneous abortions conceived from varying assisted reproductive technology procedures. Mol Cytogenet. 2016;9:79.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Bianco K, Caughey AB, Shaffer BL, Davis R, Norton ME. History of miscarriage and increased incidence of fetal aneuploidy in subsequent pregnancy. Obstet Gynecol. 2006;107:1098–102.CrossRefPubMed Bianco K, Caughey AB, Shaffer BL, Davis R, Norton ME. History of miscarriage and increased incidence of fetal aneuploidy in subsequent pregnancy. Obstet Gynecol. 2006;107:1098–102.CrossRefPubMed
5.
Zurück zum Zitat Blakemore KJ, Watson MS, Samuelson J, Dreg WR, Mahoney MJ. A method of processing first-trimester chorionic villous biopsies for cytogenetic analysis. Am J Hum Genet. 1984;36:1386–93.PubMedPubMedCentral Blakemore KJ, Watson MS, Samuelson J, Dreg WR, Mahoney MJ. A method of processing first-trimester chorionic villous biopsies for cytogenetic analysis. Am J Hum Genet. 1984;36:1386–93.PubMedPubMedCentral
6.
Zurück zum Zitat Zhang YX, Zhang YP, Gu Y, Guan FG, Li SL, et al. Genetic analysis of first-trimester miscarriages with a combination of cytogenetic karyotyping, microsatellite genotyping and arrayCGH. Clin Genet. 2009;75:133–40.CrossRefPubMed Zhang YX, Zhang YP, Gu Y, Guan FG, Li SL, et al. Genetic analysis of first-trimester miscarriages with a combination of cytogenetic karyotyping, microsatellite genotyping and arrayCGH. Clin Genet. 2009;75:133–40.CrossRefPubMed
7.
Zurück zum Zitat Dhillon RK, Hillman SC, Morris RK, McMullan D, Williams D, et al. Additional information from chromosomal microarray analysis (CMA) over conventional karyotyping when diagnosing chromosomal abnormalities in miscarriage: a systematic review and meta-analysis. BJOG. 2014;121:11–21.CrossRefPubMed Dhillon RK, Hillman SC, Morris RK, McMullan D, Williams D, et al. Additional information from chromosomal microarray analysis (CMA) over conventional karyotyping when diagnosing chromosomal abnormalities in miscarriage: a systematic review and meta-analysis. BJOG. 2014;121:11–21.CrossRefPubMed
8.
Zurück zum Zitat Shimokawa O, Harada N, Miyake N, Satoh K, Mizuguchi T. Array comparative genomic hybridization analysis in first-trimester spontaneous abortions with 'normal' karyotypes. Am J Med Genet A. 2006;140:1931–5.CrossRefPubMed Shimokawa O, Harada N, Miyake N, Satoh K, Mizuguchi T. Array comparative genomic hybridization analysis in first-trimester spontaneous abortions with 'normal' karyotypes. Am J Med Genet A. 2006;140:1931–5.CrossRefPubMed
9.
Zurück zum Zitat Lin SB, Xie YJ, Chen Z, Zhou Y, JZ W, et al. Improved assay performance of single nucleotide polymorphism array over conventional karyotyping in analyzing products of conception. J Chin Med Assoc. 2015;78:408–13.CrossRefPubMed Lin SB, Xie YJ, Chen Z, Zhou Y, JZ W, et al. Improved assay performance of single nucleotide polymorphism array over conventional karyotyping in analyzing products of conception. J Chin Med Assoc. 2015;78:408–13.CrossRefPubMed
10.
Zurück zum Zitat Sahoo T, Dzidic N, Strecker MN, Commander S, Travis MK, et al. Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: outcomes, benefits, and challenges. Genet Med. 2017;19:83–9.CrossRefPubMed Sahoo T, Dzidic N, Strecker MN, Commander S, Travis MK, et al. Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: outcomes, benefits, and challenges. Genet Med. 2017;19:83–9.CrossRefPubMed
11.
Zurück zum Zitat Rajcan-Separovich E. Chromosome microarrays in human reproduction. Hum Reprod Update. 2012;18:555–67.CrossRef Rajcan-Separovich E. Chromosome microarrays in human reproduction. Hum Reprod Update. 2012;18:555–67.CrossRef
12.
Zurück zum Zitat Shetty S, Gogate A, Gogate S, Malet P. A reproducible modified method for direct preparation of chorionic villi cytogenetic analysis. Methods Cell Sci. 2003;25:149–54.CrossRefPubMed Shetty S, Gogate A, Gogate S, Malet P. A reproducible modified method for direct preparation of chorionic villi cytogenetic analysis. Methods Cell Sci. 2003;25:149–54.CrossRefPubMed
13.
Zurück zum Zitat Rooney D. Human cytogenetics: constitutional analysis. A practical approach. 3rd ed. Oxford: University Press; 2001. Rooney D. Human cytogenetics: constitutional analysis. A practical approach. 3rd ed. Oxford: University Press; 2001.
14.
Zurück zum Zitat Doria S, Carvalho F, Ramalho C, Lima V, Francisco T, et al. An efficient protocol for the detection of chromosomal abnormalities in spontaneous miscarriages or foetal deaths. Eur J Obstet Gynecol Reprod Biol. 2009;147:144–50.CrossRefPubMed Doria S, Carvalho F, Ramalho C, Lima V, Francisco T, et al. An efficient protocol for the detection of chromosomal abnormalities in spontaneous miscarriages or foetal deaths. Eur J Obstet Gynecol Reprod Biol. 2009;147:144–50.CrossRefPubMed
15.
Zurück zum Zitat Kroon B, Harrison K, Martin N, Wong B, Yazdani A. Miscarriage karyotype and its relationship with maternal body mass index, age and mode of conception. Fertil Steril. 2011;95:1827–9.CrossRefPubMed Kroon B, Harrison K, Martin N, Wong B, Yazdani A. Miscarriage karyotype and its relationship with maternal body mass index, age and mode of conception. Fertil Steril. 2011;95:1827–9.CrossRefPubMed
16.
Zurück zum Zitat Petracchi F, Colaci DS, Igarzabal L, Gadow E. Cytogenetic analysis of first trimester pregnancy loss. Int J Gynaecol Obstet. 2009;104:243–4.CrossRefPubMed Petracchi F, Colaci DS, Igarzabal L, Gadow E. Cytogenetic analysis of first trimester pregnancy loss. Int J Gynaecol Obstet. 2009;104:243–4.CrossRefPubMed
17.
Zurück zum Zitat Choi TY, Lee HM, Park WK, Jeong SY, Moon HS. Spontaneous abortion and recurrent miscarriage: a comparison of cytogenetic diagnosis in 250 cases. Obstet Gynecol Sci. 2014;57:518–25.CrossRefPubMedPubMedCentral Choi TY, Lee HM, Park WK, Jeong SY, Moon HS. Spontaneous abortion and recurrent miscarriage: a comparison of cytogenetic diagnosis in 250 cases. Obstet Gynecol Sci. 2014;57:518–25.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Shearer BM, Thorland EC, Carlson AW, Jalal SM, Ketterling RP. Reflex fluorescent in situ hybridization testing for unsuccessful product of conception cultures: a retrospective analysis of 5555 samples attempted by conventional cytogenetics and fluorescent in situ hybridization. Genet Med. 2011;13:545–52.CrossRefPubMed Shearer BM, Thorland EC, Carlson AW, Jalal SM, Ketterling RP. Reflex fluorescent in situ hybridization testing for unsuccessful product of conception cultures: a retrospective analysis of 5555 samples attempted by conventional cytogenetics and fluorescent in situ hybridization. Genet Med. 2011;13:545–52.CrossRefPubMed
19.
Zurück zum Zitat Lathi RB, Milki AA. Rate of aneuploidy in miscarriages following in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril. 2004;81:1270–2.CrossRefPubMed Lathi RB, Milki AA. Rate of aneuploidy in miscarriages following in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril. 2004;81:1270–2.CrossRefPubMed
20.
Zurück zum Zitat Menasha J, Levy B, Hirschhorn K, Kardon NB. Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from f 12-year study. Genet Med. 2005;7:251–63.CrossRefPubMed Menasha J, Levy B, Hirschhorn K, Kardon NB. Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from f 12-year study. Genet Med. 2005;7:251–63.CrossRefPubMed
21.
Zurück zum Zitat Rodriguez-Purata J, Lee J, Whitehouse M, Moschini RM, Knopman J, et al. Embryo selection versus natural selection: how do outcomes of comprehensive chromosome screening of blastocysts compare with the analysis of products of conception from early pregnancy loss (dilation and curettage) among an assisted reproductive technology population? Fertil Steril. 2015;104:1460–6.CrossRefPubMed Rodriguez-Purata J, Lee J, Whitehouse M, Moschini RM, Knopman J, et al. Embryo selection versus natural selection: how do outcomes of comprehensive chromosome screening of blastocysts compare with the analysis of products of conception from early pregnancy loss (dilation and curettage) among an assisted reproductive technology population? Fertil Steril. 2015;104:1460–6.CrossRefPubMed
22.
Zurück zum Zitat Lomax B, Tang S, Separovic E, Phillips D, Hillard E, et al. Comparative genomic hybridization in combination with flow cytometry improves results of cytogenetic analysis of spontaneous abortions. Am J Hum Genet. 2000;66:1516–21.CrossRefPubMedPubMedCentral Lomax B, Tang S, Separovic E, Phillips D, Hillard E, et al. Comparative genomic hybridization in combination with flow cytometry improves results of cytogenetic analysis of spontaneous abortions. Am J Hum Genet. 2000;66:1516–21.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Subramaniyam S, Pulijaal VR, Mathew S. Double and multiple chromosomal aneuploidies in spontaneous abortions: a single institutional experience. 2014:7;262–268. Subramaniyam S, Pulijaal VR, Mathew S. Double and multiple chromosomal aneuploidies in spontaneous abortions: a single institutional experience. 2014:7;262–268.
24.
Zurück zum Zitat Bettio D, Venci A, Levi Setti PE. Chromosomal abnormalities in miscarriages after different assisted reproduction procedures. Placenta. 2008; Suppl B:126–8. Bettio D, Venci A, Levi Setti PE. Chromosomal abnormalities in miscarriages after different assisted reproduction procedures. Placenta. 2008; Suppl B:126–8.
25.
Zurück zum Zitat Demko ZP, Simon AL, McCoy RC, Petrov DA, Rabinowitz M. Effects of maternal age on euploidy rates in a large cohort of embryos analyzed with 24-chromosome single-nucleotide polymorphism-based preimplantation genetic screening. Fertil Steril. 2016;105:1307–13.CrossRefPubMed Demko ZP, Simon AL, McCoy RC, Petrov DA, Rabinowitz M. Effects of maternal age on euploidy rates in a large cohort of embryos analyzed with 24-chromosome single-nucleotide polymorphism-based preimplantation genetic screening. Fertil Steril. 2016;105:1307–13.CrossRefPubMed
26.
Zurück zum Zitat Franasiak JM, Forman EJ, Hong KH, Werner MD, Upham KM, et al. The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil Steril. 2011;101:656–63.CrossRef Franasiak JM, Forman EJ, Hong KH, Werner MD, Upham KM, et al. The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil Steril. 2011;101:656–63.CrossRef
28.
Zurück zum Zitat Lathi RB, Gustin S, Keller J, Maisenbacher MK, Siqurjonsson S, et al. Reability of 46,XX results on miscarriage specimens: a review of 1,222 first trimester miscarriage specimens. Fertil Steril. 2014;101:178–82.CrossRefPubMed Lathi RB, Gustin S, Keller J, Maisenbacher MK, Siqurjonsson S, et al. Reability of 46,XX results on miscarriage specimens: a review of 1,222 first trimester miscarriage specimens. Fertil Steril. 2014;101:178–82.CrossRefPubMed
29.
Zurück zum Zitat Neusser M, Rogenhofer N, Dürl S, Ochsenkühn R, Trottmann M. Increased chromosome 16 disomy rates in human spermatozoa and recurrent spontaneous abortions. Fertil Steril. 2015;104:1130–7.CrossRefPubMed Neusser M, Rogenhofer N, Dürl S, Ochsenkühn R, Trottmann M. Increased chromosome 16 disomy rates in human spermatozoa and recurrent spontaneous abortions. Fertil Steril. 2015;104:1130–7.CrossRefPubMed
30.
Zurück zum Zitat Nagaishi M, Yamamoto T, Iinuma K, Shimomura K, Berend SA, et al. Chromosome abnormalities identified in 347 spontaneous abortions collected in Japan. J Obstet Gynaecol Res. 2004;30:237–41.CrossRefPubMed Nagaishi M, Yamamoto T, Iinuma K, Shimomura K, Berend SA, et al. Chromosome abnormalities identified in 347 spontaneous abortions collected in Japan. J Obstet Gynaecol Res. 2004;30:237–41.CrossRefPubMed
31.
Zurück zum Zitat Fragouli E, Alfarawati S, Spath K, Jaroudi S, Sarasa J, et al. The origin and impact of embryonic aneuploidy. Hum Genet. 2013;132:1001–13.CrossRefPubMed Fragouli E, Alfarawati S, Spath K, Jaroudi S, Sarasa J, et al. The origin and impact of embryonic aneuploidy. Hum Genet. 2013;132:1001–13.CrossRefPubMed
32.
Zurück zum Zitat Pellestor F, Anahory T, Hamamah S. The chromosomal analysis of human oocytes. An overview of established procedures. Hum Reprod Update. 2005;11:15–32.CrossRefPubMed Pellestor F, Anahory T, Hamamah S. The chromosomal analysis of human oocytes. An overview of established procedures. Hum Reprod Update. 2005;11:15–32.CrossRefPubMed
33.
Zurück zum Zitat Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, et al. Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006;440:497–500.CrossRefPubMed Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, et al. Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006;440:497–500.CrossRefPubMed
34.
Zurück zum Zitat Hassold T, Arnovitz K, Jacobs PA, May K, Robinson D. The parental origin of the missing or additional chromosome in 45,X and 47,XXX females. Birth Defects Orig Artic Ser. 1990;26:297–304.PubMed Hassold T, Arnovitz K, Jacobs PA, May K, Robinson D. The parental origin of the missing or additional chromosome in 45,X and 47,XXX females. Birth Defects Orig Artic Ser. 1990;26:297–304.PubMed
35.
Zurück zum Zitat Nagaoka SI, Hassold TJ, Hunt PA. Human aneuploidy: mechanism and new insights into age-old problem. Nat Rev Genet. 2013;13:493–504.CrossRef Nagaoka SI, Hassold TJ, Hunt PA. Human aneuploidy: mechanism and new insights into age-old problem. Nat Rev Genet. 2013;13:493–504.CrossRef
36.
Zurück zum Zitat Hassold T, Hunt P. To err (meiotically) is human: the genetics of human aneuploidy. Nat Rev Genet. 2001;2:280–91.CrossRefPubMed Hassold T, Hunt P. To err (meiotically) is human: the genetics of human aneuploidy. Nat Rev Genet. 2001;2:280–91.CrossRefPubMed
37.
Zurück zum Zitat Li S, Hassed S, Mulvihill JJ, Nair AK, Hopcus DJ. Double trisomy. AJMG. 2004;124A:96–8.CrossRef Li S, Hassed S, Mulvihill JJ, Nair AK, Hopcus DJ. Double trisomy. AJMG. 2004;124A:96–8.CrossRef
38.
Zurück zum Zitat Qy L, Tsukishiro S, Nakagawa C, Tanemura M, Sugiura-Ogasawa M, et al. Paternal origin and cell stage of non-disjunction of double trisomy in spontaneous abortion. Congenit Anom (Kyoto). 2005;45:21–5.CrossRef Qy L, Tsukishiro S, Nakagawa C, Tanemura M, Sugiura-Ogasawa M, et al. Paternal origin and cell stage of non-disjunction of double trisomy in spontaneous abortion. Congenit Anom (Kyoto). 2005;45:21–5.CrossRef
39.
Zurück zum Zitat Bernardini L, Gianaroli L, Fortini D, Conte N, Magli C, et al. Frequency of hyper-, hypohaploidy and diplody in ejaculate, epididymal and testicular germ cells of infertile patients. Hum Reprod. 2000;15:2165–72.CrossRefPubMed Bernardini L, Gianaroli L, Fortini D, Conte N, Magli C, et al. Frequency of hyper-, hypohaploidy and diplody in ejaculate, epididymal and testicular germ cells of infertile patients. Hum Reprod. 2000;15:2165–72.CrossRefPubMed
40.
Zurück zum Zitat Durak Aras B, Aras I, Can C, Topak C, Dikogly E, et al. Exploring the relationship between the severity of oligozoospermia and the frequencies of sperm chromosome aneuploidies. Andrologia. 2012;44:416–22.CrossRefPubMed Durak Aras B, Aras I, Can C, Topak C, Dikogly E, et al. Exploring the relationship between the severity of oligozoospermia and the frequencies of sperm chromosome aneuploidies. Andrologia. 2012;44:416–22.CrossRefPubMed
Metadaten
Titel
Chromosomal abnormalities in products of conception of first-trimester miscarriages detected by conventional cytogenetic analysis: a review of 1000 cases
verfasst von
Larysa Y. Pylyp
Lyudmyla O. Spynenko
Nataliya V. Verhoglyad
Anna O. Mishenko
Dmytro O. Mykytenko
Valery D. Zukin
Publikationsdatum
30.10.2017
Verlag
Springer US
Erschienen in
Journal of Assisted Reproduction and Genetics / Ausgabe 2/2018
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-017-1069-1

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